Characterization of Renin-Angiotensin-System at patients with Empagliflozin therapy and Angiotensin-converting enzyme inhibition.

Effect of empagliflozin on the renin-angiotensin system in patients with chronic kidney disease with and without type 2 diabetes - EMPagliflozin and RAs in kidney disease

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2016-002935-14-AT

Enrollment

Registered

2016-10-11

Start date

2016-11-22

Completion date

Unknown

Last updated

2019-12-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic kidney disease with and without type 2 diabetes MedDRA version: 20.0 Level: LLT Classification code 10076411 Term: Chronic kidney disease stage 4 System Organ Class: 100000004857 MedDRA version: 20.0 Level: LLT Classification code 10076410 Term: Chronic kidney disease stage 3 System Organ Class: 100000004857

Interventions

Trade Name: Jardiance Product Name: Empagliflozin Pharmaceutical Form: Tablet INN or Proposed INN: Empagliflozin CAS Number: 864070-44-0

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: CKD patients with type 2 diabetes • Estimated GFR (calculated with the MDRD formula) between 15 and 59 ml/min (with CKD stage IIIa/b to IV) • Albumin excretion rates of >30 mg/24 hours (UACR >30 mg/g) • Fasting plasma glucose levels >126 mg/dl [7mmol/L] or HbA1c levels >6.5% (Definition of type 2 diabetes according to the diagnostic criteria set forth by the American Diabetes Association in 2009) CKD patients without diabetes • Estimated GFR (calculated with the MDRD formula) between 15 and 59 ml/min (with CKD stage IIIa/b to IV) • Albumin excretion rates of >30 mg/24 hours (UACR >30 mg/g) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 18 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30

Exclusion criteria

Exclusion criteria: CKD patients with type 2 diabetes • Age <18 years • Severely impaired renal function (eGFR <15ml/min) • Hyperkalemia above 5,1mmol/L • Hypotension (systolic blood pressure lower than 120 mmHg on ambulatory measurement) • Pregnant patients • Patients planning pregnancy • Body mass index < 18.5 kg/m2 • Total urinary protein excretion = 3.5 g/d CKD patients without diabetes • Age <18 years • Diabetic kidney disease • Severely impaired renal function (eGFR <15ml/min) • Hyperkalemia above 5.1mmol/L • Hypotension (systolic blood pressure lower than 120 mmHg on ambulatory measurement) • Pregnant patients • Patients planning pregnancy • Body mass index < 18.5 kg/m2 • Total urinary protein excretion = 3.5 g/d

Design outcomes

Primary

Measure	Time frame
Primary end point(s): Primary endpoint will be the difference of the extent of Ang 1-7 upregulation determined by mass-spectrometric measurement of Ang 1-7 concentrations after a 3-month treatment with empagliflozin in addition to ACEi treatment alone.;Timepoint(s) of evaluation of this end point: after a three-month intake of empagliflozin.;Main Objective: The difference of Ang 1-7 increase from baseline between a 3-month treatment with empagliflozin on top of ACEi treatment compared to ACEi treatment alone; Secondary Objective: The following parameters will be assessed after 3 months of empagliflozin treatment: • Mean quantitative changes of baseline multiple RAS effector angiotensin levels • Mean changes of baseline Ang II levels • Mean changes of baseline specific protein amount on HDL • Mean changes in specific renal parameters from baseline and after 3 months of empagaliflozin treatment (albuminuria reduction, renal function) • Mean changes from baseline relevant blood parameters (HbA1c, ß-hydroxybutyrat, elektrolytes, lipids, etc.) • Mean changes from baseline urinary electrolyte levels and after 3 months of empagaliflozin treatment • Mean changes from baseline urinary RAS metabolites (angiotensinogen, ACE and ACE2 levels, ACE2 activity) • Mean changes in baseline blood pressure • Mean changes in baseline body weight • Mean changes in body fluid status • Mean changes in baseline OCR and ECAR in PBMCs • Mean changes in salt sensitivity	—

Measure

Time frame

Primary end point(s): Primary endpoint will be the difference of the extent of Ang 1-7 upregulation determined by mass-spectrometric measurement of Ang 1-7 concentrations after a 3-month treatment with empagliflozin in addition to ACEi treatment alone.;Timepoint(s) of evaluation of this end point: after a three-month intake of empagliflozin.;Main Objective: The difference of Ang 1-7 increase from baseline between a 3-month treatment with empagliflozin on top of ACEi treatment compared to ACEi treatment alone; Secondary Objective: The following parameters will be assessed after 3 months of empagliflozin treatment: • Mean quantitative changes of baseline multiple RAS effector angiotensin levels • Mean changes of baseline Ang II levels • Mean changes of baseline specific protein amount on HDL • Mean changes in specific renal parameters from baseline and after 3 months of empagaliflozin treatment (albuminuria reduction, renal function) • Mean changes from baseline relevant blood parameters (HbA1c, ß-hydroxybutyrat, elektrolytes, lipids, etc.) • Mean changes from baseline urinary electrolyte levels and after 3 months of empagaliflozin treatment • Mean changes from baseline urinary RAS metabolites (angiotensinogen, ACE and ACE2 levels, ACE2 activity) • Mean changes in baseline blood pressure • Mean changes in baseline body weight • Mean changes in body fluid status • Mean changes in baseline OCR and ECAR in PBMCs • Mean changes in salt sensitivity

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Secondary

Measure	Time frame
Secondary end point(s): • Mean quantitative changes of baseline multiple RAS effector angiotensin levels after 3 months of empagaliflozin treatment • Mean changes of baseline Ang II levels after 3 months of empagaliflozin treatment • Mean changes of baseline specific protein amount on HDL after 3 months of empagaliflozin treatment • Mean changes in specific renal parameters from baseline and after 3 months of empagaliflozin treatment (albuminuria reduction, renal function) • Mean changes from baseline relevant blood parameters (HbA1c, ß-hydroxybutyrat, elektrolytes, lipids, etc.) after 3 months of empagaliflozin treatment • Mean changes from baseline urinary electrolyte levels and after 3 months of empagaliflozin treatment • Mean changes from baseline urinary RAS metabolites (angiotensinogen, ACE and ACE2 levels, ACE2 activity) after 3 months of empagaliflozin treatment • Mean changes in baseline blood pressure after 3 months of empagaliflozin treatment • Mean changes in baseline body weight after 3 months of empagaliflozin treatment • Mean changes in body fluid status after 3 months of empagaliflozin treatment • Mean changes in baseline oxygen consumption rate (OCR) and the extracellular acidification rate (ECAR) in peripheral peripheral blood mononuclear cells (PBMCs) after 3 months of empagliflozin treatment • Mean changes in salt sensitivity after 3 months of empagliflozin treatment ;Timepoint(s) of evaluation of this end point: after a three-month intake of empagliflozin.	—

Measure

Time frame

Secondary end point(s): • Mean quantitative changes of baseline multiple RAS effector angiotensin levels after 3 months of empagaliflozin treatment • Mean changes of baseline Ang II levels after 3 months of empagaliflozin treatment • Mean changes of baseline specific protein amount on HDL after 3 months of empagaliflozin treatment • Mean changes in specific renal parameters from baseline and after 3 months of empagaliflozin treatment (albuminuria reduction, renal function) • Mean changes from baseline relevant blood parameters (HbA1c, ß-hydroxybutyrat, elektrolytes, lipids, etc.) after 3 months of empagaliflozin treatment • Mean changes from baseline urinary electrolyte levels and after 3 months of empagaliflozin treatment • Mean changes from baseline urinary RAS metabolites (angiotensinogen, ACE and ACE2 levels, ACE2 activity) after 3 months of empagaliflozin treatment • Mean changes in baseline blood pressure after 3 months of empagaliflozin treatment • Mean changes in baseline body weight after 3 months of empagaliflozin treatment • Mean changes in body fluid status after 3 months of empagaliflozin treatment • Mean changes in baseline oxygen consumption rate (OCR) and the extracellular acidification rate (ECAR) in peripheral peripheral blood mononuclear cells (PBMCs) after 3 months of empagliflozin treatment • Mean changes in salt sensitivity after 3 months of empagliflozin treatment ;Timepoint(s) of evaluation of this end point: after a three-month intake of empagliflozin.

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Countries

Austria

Contacts

Public ContactDoz. Dr. Manfred Hecking

Medical University of Vienna, Internal Medicine III, Clinical Div. of Nephrology and Dialysis

manfred.hecking@meduniwien.ac.at00431 40400 5930

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026